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CASE REPORT Open Access
Pancreatic adenocarcinoma-associatedpolymyositis treated with
corticosteroids alongwith cancer specific treatment: case
reportJohn Syrios1, Georgios Kechagias1, Ioannis D Xynos1, Maria N
Gamaletsou1, Aristea Papageorgiou1,George Agrogiannis2 and Nicolas
Tsavaris1*
Abstract
Background: Adenocarcinoma of the pancreas only rarely is
associated with inflammatory myopathy. In thissetting, polymyositis
may be treated with glucocorticoids in combination with cancer
specific treatment.
Case presentation: We present the case of a 52-year-old man with
stage IIA pancreatic tail adenocarcinoma whounderwent surgical
treatment and six months into therapy with gemcitabine he developed
symmetrical, painful,proximal muscle weakness with peripheral
oedema. Re-evaluation with imaging modalities, muscle histology
andbiochemistry conferred the diagnosis of polymyositis associated
with pancreatic cancer progression. The patientwas treated with
glucocorticoids along with gemcitabine and erlotinib which resulted
in complete remissionwithin six months. He remained in good health
for a further six months on erlotinib maintenance therapy when anew
computer tomography scan showed pancreatic cancer relapse and hence
prompted 2nd line chemotherapywith gemcitabine.
Conclusions: Polymyositis associated with pancreatic cancer may
respond to glucocorticoids along with cancerspecific treatment.
BackgroundIn developed countries, pancreatic adenocarcinoma
isthe fourth leading cause of cancer death, with an overall5-year
survival rate of less than 10% [1] and the inci-dence appears to be
increasing. Despite the advances inchemotherapy, particularly
gemcitabine, and the devel-opment of new tyrosine kinase
inhibitors, such as erloti-nib (Tarceva) an epidermal growth factor
receptor(EGFR) inhibitor, the prognosis for patients with
pan-creatic cancer is dismal[1].An association between malignancy
and inflammatory
myopathy was suspected as early as 1916, with adeno-carcinomas
of the cervix, lung, ovaries, pancreas, blad-der, and stomach
accounting for approximately 70percent of the cancers associated
with inflammatorymyopathies[2]. On the other hand, patients
with
inflammatory myopathies, which commonly include der-matomyositis
and polymyositis, have a clearly higherrisk of cancer than the
general population. Moreover,when inflammatory myopathies present
with a signifi-cant weakness at diagnosis, they carry an
unfavorableimpact on prognosis[2-4].Herewith we present a case of
polymyositis complicat-
ing the physical history of a patient with pancreatic
ade-nocarcinoma on treatment with gemcitabine whoresponded well to
glucocorticoids along with cancer spe-cific treatment.
Case presentationIn March 2009, a 52-year-old Caucasian man,
smoker30 pack/y, with type II diabetes presented with a
recenthistory of recurrent acute pancreatitis and significantweight
loss (15 kg over 3 mo). Computer Tomography(CT) examination
revealed a solitary mass lesion in thepancreatic tail and the
patient subsequently underwentdistal pancreatectomy coupled with
splenectomy. Patho-logic examination of the resected specimens
conferred
* Correspondence: [email protected] of
Pathophysiology, Laiko General Hospital, Medical School,National
and Kapodistrian University of Athens, Mikras Asias 75,
11527Athens, GreeceFull list of author information is available at
the end of the article
Syrios et al. BMC Gastroenterology 2011,
11:33http://www.biomedcentral.com/1471-230X/11/33
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Open Access article distributed under the terms of the Creative
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(http://creativecommons.org/licenses/by/2.0), which permits
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the diagnosis of a poorly differentiated adenocarcinomawhich was
locally invasive to the peripancreatic adiposetissue. Lymph nodes
were negative and surgical marginswere clear (T.N.M. stage IIA).
The patient was treatedwith sequential adjuvant chemotherapy, six
cycles ofgemcitabine (1000 mg/m2) on days 1, 8, 15 and every28 d
with a steady decline of CA 19.9 levels. Six monthsinto treatment
with gemcitabine he developed symmetri-cal, painful, proximal
muscle weakness in the upper andlower limbs with peripheral oedema
and significantpain. The symptoms were severe enough to have
con-fined him to a wheelchair.On readmission to hospital physical
signs and history
suggested the diagnosis of polymyositis. Aspartate
ami-notrasferase (AST) was 103 U/L (normal 5-40),
alanineaminotrasferase (ALT) 77 U/L (normal 5-40), creatininekinase
(CK) 595 U/L (normal 40-150), lactate dehydro-genase (LDH) 556 U/L
(normal 200-460), C-reactiveprotein (CRP) 560 nmol/L (normal
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malignancy[5,6]. Hill et al[6] identified that 137 out of914
cases of polymyositis had cancer, and reported thatthe standardized
incidence ratio - SIR was 1.4 (95% CI1.0-1.8) for men and 1.2
(0.9-1.6) for women. Polymyosi-tis was associated with a raised
risk of non-Hodgkin lym-phoma, lung and bladder cancers, but not of
pancreaticcancer. Sigurgeirsson et al[2] further sustained
thatinflammatory myopathy is strongly associated withmalignancy and
the malignant diseases most associatedwith inflammatory myositis
were, in descending order:lung cancer, rectum and colon cancer,
pancreatic cancer,kidney cancer, stomach cancer, breast cancer and
Car-penter et al[3] reported poor prognosis when
significantweakness is experienced at presentation.Our patient was
diagnosed with high grade, pancrea-
tic-tail adenocarcinoma and six months following diag-nosis and
surgical resection, presented with proximalsymmetrical muscle
weakness, myalgias and generalisedoedema while on treatment with
gemcitabine. Thesesigns were alarmingly suspicious of inflammatory
myo-pathy and prompted further specific investigations.Eventually,
diagnosis was confirmed with blood bio-chemistry, electromyography
and muscle histology onthe basis of a highly compatible history and
physicalfindings.According to Bohan and Peter’s criteria[5],
polymyosi-
tis is an inflammatory myopathy with no rash. It isdefined by
symmetric proximal muscle weakness, ele-vated serum muscle enzymes,
myopathic changes on
electromyography, characteristic muscle biopsy abnorm-alities
and the absence of histopathologic signs of othermyopathies. Muscle
weakness is indeed the most com-mon presenting feature of
polymyositis. The onset isusually insidious and the distribution of
weakness istypically symmetric and proximal. Myalgias occurs inless
than 30% of the patiens[7].Serum muscle enzyme levels are usually
elevated in
patients with polymyositis including CK, LDH, aldolase,AST and
ALT which are routinely measured in the eva-luation of myopathy.
Although most patients with poly-myositis have increased CK levels,
reported seriesinclude patients with normal CK levels at
presentation[8]. Specific autoantibodies such as those
directedagainst cytoplasmic RNA synthetases, other
cytoplasmicproteins, ribonucleoproteins, and certain nuclear
anti-gens play important role in the assessment of patientswith
polymyositis given that they occur in approximately30 percent of
patients with polymyositis[9]. In additionto these, a novel
autoantibody to a 155 kd protein (anti-p155) is commonly found in
cancer associated dermato-myositis, but not in cancer associated
polymyositis[10].Even in clinical scenarios consistent with
polymyositis,
muscle biopsy is essential to establish the diagnosis.Typically,
the cellular infiltrate is predominantly withinthe fascicle with
inflammatory cells invading individualmuscle fibers. Abnormal
muscle fibers are scatteredthroughout the fascicle. Furthermore,
there is evidenceof cell-mediated immune mechanisms with presence
ofcytotoxic CD8+ T cells, which recognize antigens on themuscle
fiber surface, and enhanced expression of majorhistocompatibility
complex (MHC) antigens by the mus-cle fibers[11].Although the
scenario of gemcitabine induced myosi-
tis cannot be entirely excluded in our case, this appearsto be
highly unlikely; we found just one case report inthe literature[12]
implicating gemcitabine given alongwith docetaxel in inflammatory
myopathy in a patientwith lung adenocarcinoma and nevertheless as
myositisin our patient heralded disease progression, it was fairto
assume that it was disease rather than drug inducedand thus
necessitated standard immunosuppressivetreatment along with cancer
specific therapy. Subse-quently, a dramatic clinical response was
observed andthe patient was ambulatory and fully recovered.
Bio-chemical parameters normalised shortly after treatmentwith
intravenous glucocorticoids and maintenance treat-ment with oral
corticosteroids coupled with gemcitabineand erlotinib conferred
complete response.Glucocorticoids are indeed the cornerstone of
initial
therapy for polymyositis but in severely ill
patients,azathioprine or methotrexate is preferable. The treat-ment
of choice is prednisone in tapering doses forapproximately one
year, depending upon patient’s
Figure 3 Abdominal PET/CT. Figure 2. PET/CT fusion image
takensix months into treatment with erlotinib and
corticosteroidsshowing postoperative findings only. There is no
increased uptakeof 18F-FDG.
Syrios et al. BMC Gastroenterology 2011,
11:33http://www.biomedcentral.com/1471-230X/11/33
Page 3 of 5
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response to therapy and achievement of disease
control.Nevertheless, as many as 50% of patients with polymyo-sitis
do not respond to glucocorticoid therapy alone[2,13]. However in
paraneoplastic polymyositis it is diffi-cult to evaluate whether
the clinical response of myositisis due to glucocorticoids per se
or to the concurrent useof immunosuppressive chemotherapy or due to
a syner-gistic effect among them.Giving an insight in the
pancreatic tumor cell, there
are several immunogenic tumor antigens to elicit cellu-lar as
well as humoral immunity. In the Okada et alstudy[14], two DNA
mismatch repair enzymes, Homosapiens mutS homolog 2 (hMSH2) and
Homo sapienspostmeiotic segregation increased 1 (hPMS1) werefound
to over-express in pancreatic ductal adenocarci-noma, and their
antibodies were detected in sera frompatients with pancreatic
ductal adenocarcinoma, and insera from patients with polymyositis,
but not in serafrom healthy individuals. Therefore, hMSH2 and
hPMS1could be immunogenic antigens in patients with pan-creatic
adenocarcinoma. Additionally Egberts et alshowed that dexamethasone
treatment had profoundinfluence of pancreatic duct adenocarcinoma
cells invitro in terms of inhibition of invasiveness and
activationof NF�B which was approved in vivo by reduced
metas-tasing capability and reduced size of local tumour
recur-rence in an experimental model of pancreatic cancer[15].
These observations indicate that the link betweenmalignancy and
inflammatory myopathy relates possiblyto the expression of common
autoantigens between can-cer tissue and muscle tissue in some
patients with poly-myositis. From a therapeutic point of view
treatmentwith glucocorticoids should be justified in confirmedcases
of polymyositis associated with pancreatic canceralong with cancer
specific therapy. In addition ourexperience reinforces the basis
for adjuvant immu-notherapy as a potential additional therapeutic
modalityfor all patients with pancreatic cancer, a notion whichhas
been based mainly on experimental findings butappears to collect
clinical substantiation and certainlymerits further
investigation.
ConclusionsPolymyositis is a paraneoplastic syndrome which may
beencountered in patients with pancreatic cancer causingsignificant
morbidity. Clinicians should be aware of thissyndrome as it may
manifest at any stage during thephysical history of pancreatic
cancer. In this clinical set-ting a trial with corticosteroids
along with cancer speci-fic treatment may be of benefit.
ConsentWritten informed consent was obtained from the patientfor
publication of this case report and any accompanying
images. A copy of the written consent is available forreview by
the Editor-in-Chief of this journal.
Author details1Department of Pathophysiology, Laiko General
Hospital, Medical School,National and Kapodistrian University of
Athens, Mikras Asias 75, 11527Athens, Greece. 21st Department of
Pathology, Medical School, National andKapodistrian University of
Athens, Athens, Mikras Asias 75, 11527 Athens,Greece.
Authors’ contributionsJS, GK and IDX were involved in the direct
care of the patient, reviewed theliterature and drafted the
manuscript; MNG and AP are involved in thedirect care of the
patient, GA performed pathology, NT is involved in thedirect care
of the patient, coordinated the study and critically revised
themanuscript. All authors read and approved the final
manuscript.
Competing interestsThe authors declare that they have no
competing interests.
Received: 31 October 2010 Accepted: 7 April 2011Published: 7
April 2011
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Pre-publication historyThe pre-publication history for this
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here:http://www.biomedcentral.com/1471-230X/11/33/prepub
doi:10.1186/1471-230X-11-33Cite this article as: Syrios et al.:
Pancreatic adenocarcinoma-associatedpolymyositis treated with
corticosteroids along with cancer specifictreatment: case report.
BMC Gastroenterology 2011 11:33.
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AbstractBackgroundCase presentationConclusions
BackgroundCase presentationDiscussionConclusionsConsentAuthor
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